Hormone therapy Flashcards

1
Q

Some cancers are hormone sensitive because…

A

the tissues they arise from are under hormonal control of normal cellular proliferation or survival

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2
Q

Name some cancers that involve hormones

A

Prostate, breast and endometrium (sex hormones), and lymphocytic malignancies such as lymphoma, leukaemia and myeloma (corticosteriods)

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3
Q

What are the uses of hormonal treatments? (across all stages of cancer)

A
  1. To shrink the primary tumours before surgery (neoadjuvant)
  2. To prevent or delay growth of micro metastases following surgery (adjuvant)
  3. To shrink established metastases and improve quality/ duration of life (palliative)
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4
Q

what sort of hormones are most hormonal therapies?

A

Steroid hormones

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5
Q

How do steroid hormones work?

A

Steriods interact with cytoplasmic protein receptors to form functional DNA transcription factors, affecting the transcription of multiple genes

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6
Q

Where are sex hormones produced in post-menopausal women?

A

Extra-gonadal, in the fat and adrenal glands

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7
Q

How is the source of hormones stopped in pre-menopausal women?

A
Bilateral oophorectomy (outdated)
Long-acting LHRH analogues (e.g. goserelin, leuprorelin), which through receptor down-regulation in the pituitary, block LH and FSH production, and in turn gonadal hormone output
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8
Q

What are aromatase inhibitors used for?

A

To stop oestrogen production in post-menopausal women with hormone-sensitive cancers

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9
Q

How to aromatase inhibitors work?

A

The rate-limiting step in oestrogen synthesis is the conversion of androstenedione to oestrone by the enzyme aromatase.
In post-menopausal women, androstenedione is secreted by the adrenal glands and aromatized in other tissues, including the fat and liver.
This step is the target for aromatase inhibitors.

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10
Q

Name some new aromatase inhibitors

A

Anastrozole, exemstane, letrozole

Highly effective in clinical trials, with greater efficacy and different less symptomatic early toxicities

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11
Q

What do hormone inhibitors do?

A

Block hormones from binding to their receptors in tumour cells

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12
Q

How does tamoxifen work?

A

Acts in part to stop oestrogen binding to it’s receptors -used in all stages of breast cancer treatment

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13
Q

Name two classes of anti-androgen used in prostate cancer

A
  1. Steroidal anti-androgens

2. Non-steriodal anti-androgens

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14
Q

How to steroidal anti-androgens work?

A

e.g. cyproterone acetate
They have a dual action.
In tumour cells, they inhibit the androgen receptor, but in the hypothalamus they substitute it for testorsterone, so stimulate negative feedback inhibition with subsequent decrease in LHRH release.

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15
Q

How do non-steriodal anti-androgens work?

A

They inhibit testosterone in both tumour cells and the hypothalamus, so feedback inhibition is lost and serum testosterone levels rise.

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16
Q

Give an example of a steroidal anti-androgen

A

Cyproterone acetate

17
Q

Given an example of a non-steroidal anti-androgen

A

bicalutamide

18
Q

Describe what a ‘maximum androgen blockage’ entails

A

The combination of a non-steroidal anti-androgen with an LHRH analogue - used as therapeutic strategy in prostate cancer

19
Q

What is the advantage of a maximum androgen blockade over just a non-steroidal anti-androgen?

A

Prevents the rise in testosterone levels associated with non-steroidal anti-androgens.

20
Q

Why might increasing hormones sometimes be helpful?

A

Glucocorticoids in high concentration induce apoptosis in some malignancy lymphoid cells, and form an important component of treatments for lymphoid leukaemias, lymphomas, myeloma and Hodgkin’s disease

21
Q

What hormone induces apoptosis in some malignant lymphoid cells at high doses?

A

Glucocorticoids

22
Q

Why might hormone supplementation be used in treatment of sex-hormone sensitive cancers?

A

Aim to induce negative feedback loops e..g. oestrogens to down-regulate hypothalamic LHRH in prostate cancer

23
Q

What are progestogens?

A

Synthetic analogues of progesterone

24
Q

Give an example of a progestogen

A

Megestrol acetate

25
Q

When might a progestogen be used?

A

Can be given orally in high doses for cancers arising in progesterone sensitive tissues (breast, endometrium). They may give direct inhibition of tumour growth via acting as an agonist of the progesterone receptor, but also produce negative feedback on the pituitary/ gonadal axis.

26
Q

Why might progestogen drugs be used in a palliative care setting?

A

Stimulate appetite